|Year : 2019 | Volume
| Issue : 1 | Page : 27-32
Efficacy of pharmacoinvasive percutaneous coronary intervention versus primary percutaneous coronary intervention in ST elevation myocardial infarction
Ashmawy M., Sharaf El-din S., Deraz E., Mosaad A.
Department of Cardiology, Faculty of medicine, Tanta University, Egypt
|Date of Submission||14-Apr-2018|
|Date of Acceptance||03-May-2018|
|Date of Web Publication||17-Sep-2019|
01062434473, Postal code: 13731.
Background ST-segment elevation myocardial infarction (STEMI) is mainly caused by complete occlusion of a coronary artery by a thrombus. Primary percutaneous coronary intervention requires transfer to an interventional cardiology center and this delays initiation of reperfusion therapy. A pharmacoinvasive strategy may alleviate the barriers in timely reperfusion of STEMI, especially in a developing country like Egypt.
Aim The aim of the study was to assess the safety and efficacy of pharmacoinvasive strategy versus PPCI in STEMI patients at 3 months.
Patients and methods A total of 200 patients were presenting with STEMI who were divided into two groups: group 1 included patients who underwent PPCI (n=160) and group 2 included patients who underwent pharmacoinvasive strategy as patients received thrombolytic therapy followed by scheduled coronary angiography and PCI within 24 h from the symptom onset (n=40). Primary end points were death, cardiogenic shock, reinfarction, repeated revascularization of the culprit artery, and congestive heart failure at the time of discharge or at follow-up till 3 months.
Results In group 1, we found that about 28.1% of patients had infarct-related artery open and 71.9% were closed, while in group 2 there were 70.0% patients who had infarct-related artery open and 30.0% who had failed thrombolysis. There were 4.4% patients in group 1 and 75.0% patients in group 2 who were with bleeding complication especially at the access site. Complication was less frequent in group 1.
Conclusion A pharmacoinvasive strategy resulted in outcomes that were comparable with PPCI at 3 months, suggesting it might be a viable option in Egypt. Larger studies are required to confirm these findings.
Keywords: pharmacoinvasive strategy, ST elevation myocardial infarction, timely reperfusion
|How to cite this article:|
M. A, S. SE, E. D, A. M. Efficacy of pharmacoinvasive percutaneous coronary intervention versus primary percutaneous coronary intervention in ST elevation myocardial infarction. Tanta Med J 2019;47:27-32
|How to cite this URL:|
M. A, S. SE, E. D, A. M. Efficacy of pharmacoinvasive percutaneous coronary intervention versus primary percutaneous coronary intervention in ST elevation myocardial infarction. Tanta Med J [serial online] 2019 [cited 2020 Apr 8];47:27-32. Available from: http://www.tdj.eg.net/text.asp?2019/47/1/27/267023
| Introduction|| |
ST-segment elevation myocardial infarction (STEMI) is a life-threatening manifestation of coronary artery disease requiring immediate reperfusion. The incidence of STEMI is higher in Egypt when compared with other developed countries and results in significant mortality . The current recommendations maintain primary percutaneous coronary intervention (PPCI) as the treatment of choice in the management of STEMI, at centers with a skilled PCI laboratory within the suggested timelines . However, unavailability of PPCI capable hospitals in Egypt and delays in transport have restricted the access to this life-saving modality to less than 10% of patients with STEMI . Of those, patients who reached the hospital early still have to deal with other issues, such as arranging for finances, as most of the Egyptian patients pay out of pocket, even for the emergency services, such as PPCI . On the other hand, introduction of fibrin-specific lytic agents like tenecteplase (TNK) has significantly improved the infarct-related artery (IRA) patency rates . Rapid fibrinolytic treatment after STEMI improved the outcomes in patients treated within an hour of symptom onset, with decreasing benefits after 3 h . However, fibrinolysis is associated with high rates of reocclusion of IRA, so a strategy of initial bolus lysis followed by early coronary angiography and PCI within 3–24 h of fibrinolysis, now known as ‘pharmacoinvasive strategy’ ,, has been considered as a good alternative in the treatment of STEMI, especially in a developing country such as Egypt.
| Patients and methods|| |
This prospective, observational study was conducted between August 2015 and February 2016. All study centers were well equipped to handle cardiac emergencies. A total of 200 patients who fulfilled the inclusion/exclusion criteria with STEMI were enrolled in the study. Written informed consent was signed by all the patients and the study has been cleared by the ethics committees of the respective hospitals. As this is an observational study, the treatment options were chosen entirely by the patient and the attendants; hence, some patients who presented outside the recommended timelines for thrombolysis have received lytic therapy. Thrombolysis was performed in the ICU of the hospital in all centers. PCI was performed in the Cardiology Department, Tanta University Hospital. The aim of the study was to assess the safety, efficacy, and feasibility of pharmacoinvasive strategy in comparison to PPCI in patients with STEMI.
Our primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularization, and congestive heart failure (CHF), up to 3 months.
The detailed description of the statistical analysis is published previously . As this was a pilot study, primarily conducted to assess feasibility of the pharmacoinvasive strategy in STEMI patients, a sample size of 200 patients was deemed sufficient for the study. Statistical analyses were performed using the SAS software, version 9.2 (SPSS Inc., Chicago, Illinois, USA). χ2 or Mantel–Haenszel test or Fischer’s exact test was used for the observed differences between groups. Relative risk estimates with 95% confidence intervals and Kaplan–Meier curves were used to compare the differences in outcomes. A P value of 0.05 was considered significant for all the statistical evaluations.
| Results|| |
The results of this study was up to 3 months follow-up. Out of the 200 total studied patients, PPCI arm (group 1) had 160 patients and the pharmacoinvasive arm (group 2) had 40 patients. Baseline characteristics were statistically not different between both groups. In our study, we found that about 28.1% patients had IRA open and 71.9% was closed in group 1, while in group 2 there were 70.0% patients who had IRA open and 30.0% who had failed thrombolysis. There were 4.4% patients in group 1 and 75.0% patients in group 2 were bleeders especially at the access site. All patients in both groups underwent coronary angiography either immediate or scheduled with stenting. In our study, we divided the patients into patients who arrived within 0–3 h after onset of symptom and were about 47 patients in group 1 with ejection fraction (EF) ranging from 48 to 60%, mean±SD (53.65±3.49%) and 16 patients in group 2 with EF ranging from 49 to 58%, mean±SD (54.3±3.23%); it EF was slightly increased in group 2 but with no statistically significant difference between both groups (P=0.587). On the other hand, patients who arrived within 3–6 h from the onset of symptom were about 113 patients in group 1 with EF ranging from 48 to 58%, mean±SD (52.02±2.69%) and 24 patients in group 2 with EF ranging from 48 to 57%, mean±SD (50.17±1.95%) with increase in EF of patients in group 1 that was statistically significant difference between both groups (P=0.002). In our study, we divided the patients into patients who previously arrived in 0–3 h at admission and were about 47 patients in group 1 with EF at follow-up ranging from 48 to 65%, mean±SD (55.78±5.65%) at their follow-up and 16 patients in group 2 with EF ranging from 49 to 65%, mean±SD (56.21±6.17%); it was slightly increased in group 2 but with no statistically significant difference between both groups, P value of 0.798. On the other hand, patients who arrived in 3–6 h previously at the time of admission were about 113 patients in group 1 with EF ranging from 48 to 64%, mean±SD (55.29±4.79%) and 24 patients in group 2 with EF ranging from 48 to 62%, mean±SD (52.94±5.14%) with an increase in EF of patients in group 1. There was a statistically significant difference between both groups, P value of 0.033. For patients who were in arm 0–3 h, there were three patients presented with HF symptoms in group 1 and two patients in group 2, also one patient presented with anginal chest pain symptom in group 1 and one patient in group 2 with no statistically significant difference between both groups, P value of 0.511. For patients who were in arm 3–6 h there were five patients presented with HF symptoms in group 1 and five patients in group 2, also three patients presented with anginal chest pain symptom in group 1 and two patients in group 2 with statistically significant difference between both groups (P=0.006) ([Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6]).
| Discussion|| |
PPCI is considered to be the preferred method of revascularization in STEMI management where feasible. However, it is availability is limited due to various factors, especially in a developing country like Egypt. A pharmacoinvasive strategy has been studied as a valuable alternative to PPCI for STEMI ,, and can be used to prevent time lag in successful reperfusion.
In this study, 200 patients with STEMI who underwent either PPCI or a pharmacoinvasive strategy within 6 h of symptom onset were followed up until 3 months. In the primary end point, which is a composite of death, cardiogenic shock, reinfarction, repeated revascularization of the culprit artery and CHF, there was a trend toward benefit from PPCI during the early phase of follow-up, in spite of the fact that relatively affluent patients underwent PPCI; hence, this group is expected to have better long-term outcomes due to lifestyle changes and better adherence to medication.
Our results showed no statistically significant difference between both groups corresponding to the arm of 0–3 at the time of discharge and also in the follow-up after 3 months, but it is worth noticing that EF of patients in pharmacoinvasive strategy was slightly higher (54.3±3.23) than those in PPCI group (53.65±3.94), while in the follow up of patients in the arm 3–6 h, there was statistical significance between both groups with more improvement and less complication including heart failure and anginal chest pain in the group of PPCI.
STEMI represents the most dreaded form of acute coronary syndromes and therefore requires early employment of evidence-based treatment for favorable outcomes. Timely reperfusion is the key strategy in patients with STEMI and decreases mortality and major cardiovascular events. Choosing the optimal reperfusion strategy and shortening the time from symptom to reperfusion are great challenges in the practice for STEMI patients.
While PPCI is maintained as the preferred mode of reperfusion by most guidelines, only few patients with STEMI can avail this form of reperfusion within the guideline-recommended timelines.
On the other hand, fibrinolysis is fraught with dangers of reocclusion of IRA. Initial timely fibrinolysis to open the IRA and early PCI to improve the patency rates, labeled as ‘pharmacoinvasive strategy’ is an attractive option of reperfusion in STEMI and has gained momentum recently. Pharmacoinvasive strategy consists of early fibrinolysis followed by either rescue PCI for patients with failed thrombolysis or nonurgent coronary angiography to determine the need for additional revascularization within 3–24 h , and differs from a ‘facilitated’ approach which consists of an immediate PCI following fibrinolysis and has shown adverse outcomes . However, our analysis suggests that in STEMI patients presenting within 3 h after symptom onset, early reperfusion with a fibrinolytic agent before PCI reduces the risk of cardiogenic shock when compared with PPCI alone, at the cost of an increased risk of bleeding. Whether such a strategy improves long-term survival is not known .
‘STREAM’ is the first randomized trial to assess the safety and efficacy of pharmacoinvasive strategy versus PPCI in patients presenting with STEMI . Patients with STEMI were enrolled in the study if they presented within 3 h of symptom onset and were unable to undergo PPCI within 60 min of arriving at the hospital.
Fibrinolysis was done using TNK along with contemporary antiplatelet and anticoagulant therapies. A total of 1892 patients were randomized to either pharmacoinvasive group or PPCI group. The primary end point was a composite of all-cause death, shock, CHF, or reinfarction at 30 days. STREAM trial showed similar outcomes in both groups at 30 days with the primary end point occurring at 12.4% in the pharmacoinvasive group and 14.3% in the PPCI group [Risk ratio (RR)=0.86; 95% confidence interval (CI): 0.68–1.09; P=0.21]. The result was consistent across all prespecified subgroups in the study.
The overall intracranial bleeding rate was not different (0.54 vs. 0.26%, respectively; P=0.45) after the trial protocol was amended to reduce the dose of TNK in patients aged greater than or equal to 75 years. The pharmacoinvasive strategy circumvented an emergent procedure in 64% of the patients. The 1 year results of STREAM showed no difference in mortality rates between both groups 
‘STEPP-AMI’ is an observational pilot study that compared the outcomes of pharmacoinvasive versus PPCI strategies in patients with STEMI . In all, 200 patients were enrolled into the study. The primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularization of the culprit artery, and CHF at 30 days.
The primary end point occurred in 11.1% in the pharmacoinvasive group and in 3.9% in the PPCI group, P=0.07 (RR=2.87; 95% CI: 0.92–8.97). The initial trend toward benefit of PPCI narrowed over a period of 1 year (13.3 vs. 9%, RR=1.48, 95% CI: 0.60–3.62; P=0.4).
There was no difference in bleeding rates between both groups. The average total ischemic time is about 4 h in this study. More importantly, both STREAM and STEPP-AMI showed significantly higher rates of open IRA and better TIMI flow at catheterization in the pharmacoinvasive group of patients. These patients also had higher rates of referral for CABG as a part of complete revascularization.
In TRANSFER-AMI trial , 1059 patients with STEMI were randomized to either standard treatment after fibrinolysis or immediate transfer for PCI within 6 h after fibrinolysis. At 30 days. the primary end point, which is the composite of death, reinfarction, recurrent ischemia, new or worsening CHF, or cardiogenic shock, occurred in 11.0% in routine early PCI group and in17.2% in standard treatment group (RR=0.64; 95% CI: 0.47–0.87; P=0.004).
Similar results are noted from FASTMI registry , WEST , and GRACIA-2 . Data from a recent study by Gershlick et al.  also supports that in case of PCI related delay of greater than 55 min, a pharmacoinvasive strategy clearly had better outcomes than PPCI in patients presenting with STEMI.
Increasingly more data support the pharmacoinvasive strategy as an efficient therapeutic option in patients with STEMI if PPCI cannot be performed rapidly.
Fibrinolysis followed by an early coronary angiogram within 3–24 h with PCI, if appropriate, appears to be the logical solution to geographical and logistical barriers of availing a timely PPCI. It will be interesting to see if this pharmacoinvasive strategy emerges as an alternative to PPCI in the management of STEMI.
In a recent study, which was not an RCT, Kelbæk et al.  demonstrated that deferred stent implantation in STEMI is a feasible option. Thirty-eight percent of patients in that study had less than 30% residual stenosis. More interestingly, patients in group A also had better IRA patency rates and a lower thrombus burden at catheterization when compared with studies of fibrinolytic therapy in other healthcare systems and countries.
| Conclusion|| |
Pharmacoinvasive strategy produces similar 3-month clinical outcomes as PPCI in STEMI patients presented within 3 h of symptom onset. On the other hand, patients presented with 3–6 h of symptom onset who were treated with PPCI strategy have better clinical outcome comparable to pharmacoinvasive PCI. Although PPCI is more effective than fibrinolysis, the incremental benefit of PPCI is especially susceptible to treatment delays, delivery of PPCI reperfusion within the guidelines recommended times should therefore be the absolute aim. However, clearly in some scenarios delivery of PPCI within the overall ischemic times is not possible. So, pharmacoinvasive strategy as a treatment policy in STEMI is not an alternative approach to PPCI but complementary and should be considered in STEMI patients who cannot undergo PPCI with 1 h from the first medical contact.
The study had some potential limitations such as the small size of the study population, which was due to many factors, one of them that not all patients were willing to the idea of follow up after 3 months. Also, a lot of cases came with late presentation after 6 h of symptom onset and refused doing PCI due to logistic or cultural issues as well as our study included only patients with first attack STEMI And the use of bare metal stent in majority of cases due to limited facilities. Another limitation was the short period assigned for follow up which did not allow the appearance of results for mortality, reinfarction, and rehospitalization. Also, the use of M-mode or Simpson’s method might not be of the same accuracy in the assessment of global and regional LV systolic function as the newest techniques such as strain and strain rate.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS et al.
Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet 2008; 371:1435–1442.
O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA et al.
2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61:e78–e140.
Dalal JJ, Alexander T, Banerjee PS, Dayasagar V, Iyengar SS, Kerkar PG et al.
2013 consensus statement for early reperfusion and pharmaco-invasive approach in patients presenting with chest pain diagnosed as STEMI (ST elevation myocardial infarction) in an Indian setting. J Assoc Physicians India 2014; 62:473–483.
Victor SM, Gnanaraj A, Vijayakumar S, Pattabiram S, Mullasari AS et al.
Door-to-balloon: where do we lose time? Single centre experience in India. Indian Heart J 2012; 64:582–587.
Iyengar SS, Nair T, Sathyamurthi I, Hiremath JS, Jadhav U, Kumbla D et al.
Efficacy and safety of tenecteplase in STEMI patients from ELAXIM Indian registry. Indian Heart J 2009; 61:480–481.
Taher T, Fu Y, Wagner GS, Goodman SG, Fresco C, Granger CB et al.
Aborted myocardial infarction in patients with ST-segment elevation: insights from the assessment of the safety and efficacy of a new thrombolytic regimen-3 trial electrocardiographic sub-study. J Am Coll Cardiol 2004; 44:38–43.
Dauerman HL, Sobel BE. Toward a comprehensive approach to pharmacoinvasive therapy for patients with ST segment elevation acute myocardial infarction. J Thromb Thrombolysis 2012; 34:180–186.
Alexander T, Victor SM, Mullasari AS, Veerasekar G, Subramaniam K, Nallamothu B et al.
Protocol for a prospective, controlled study of assertive and timely reperfusion for patients with ST-segment elevation myocardial infarction in Tamil Nadu: the TN-STEMI programme. BMJ Open 2013; 3:e003850.
Bowers D. Medical statistics from scratch: an introduction for health professionals. UK: John Wiley & Sons; 2008.
Steg PG, James SK, Atar D, Badano LP, Biomostrom-Lundgvist C, Borger MA et al.
ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:2569–2619.
Van De Werf F. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 2006; 367:569–578.
Vanhaverbeke M, Sinnaeve P, Wan der werf F, Jannsens L et al.
Abstract 18226: fibrinolysis before percutaneous coronary intervention reduces the rate of cardiogenic shock in patients presenting within 3 h after symptom onset. Circulation 2015; 132:A18226.
Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y et al.
Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med 2013; 368:1379–1387.
Sinnaeve PR, Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Lambert Y et al.
ST-segment-elevation myocardial infarction patients randomized to a pharmaco-invasive strategy or primary percutaneous coronary intervention: Strategic Reperfusion Early After Myocardial Infarction (STREAM) 1-year mortality follow-up. Circulation 2014; 130:1139–1145.
Herrett E, George J, Denaxas S, Bhaskaran K, Timmis A, Hemingway H, Smeeth L et al.
Type and timing of heralding in ST-elevation and non-ST-elevation myocardial infarction: an analysis of prospectively collected electronic healthcare records linked to the national registry of acute coronary syndromes. Eur Heart J Acute Cardiovasc Care 2013; 2:235–245.
Cantor WJ, Fitchett D, Borgundvaag B, Ducas J, Heffernan M, Cohen E et al.
Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med 2009; 360:2705–2718.
Danchin N, Coste P, Ferrières J, Steg PG, Cottin Y, Blanchard D et al.
Comparison of thrombolysis followed by broad use of percutaneouscoronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: data from the French Registry on Acute ST-Elevation Myocardial Infarction (FASTMI). Circulation 2008; 118:268–276.
Armstrong PW, WEST Steering Committee. A comparison of pharmacologic therapy with/without timely coronary intervention vs. primary percutaneous intervention early after STelevation myocardial infarction: the WEST (Which Early ST elevation myocardial infarction therapy) study. Eur Heart J 2006; 27:1530–1538.
Fernández-Avilés F, Alonso JJ, Peña G, Blanco J, Alonso-Briales J, Lopez-Mesa J et al.
Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation:the GRACIA-2 non-inferiority, randomized, controlled trial. Eur Heart J 2007; 28:949–960.
Gershlick AH, Westerhout CM, Armstrong PW, Huber K, Halvorsen S, Steg PG et al.
Impact of a pharmacoinvasive strategy when delays to primary PCI are prolonged. Heart 2015; 101:692–698.
Kelbæk H, Engstrøm T, Ahtarovski KA, Lonborg J, Vejlstrup N, Pedersen F et al.
Deferred stent implantation in patients with ST-segment elevation myocardial infarction: a pilot study. EuroIntervention 2013; 8:1126–1133.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]